Epothilone A (EpoA) and epothilone B (EpoB) are among 16-membered cyclic epothilone compounds derived from macrocyclic lactone-based polyketone compounds. They are initially isolated from soil bacteria, Sorangium cellulosum strain So ce90, and have the structure below. [Hofle et al., 1996, Angew. Chem. Int. Ed. Engl. 35(13/14): 1567-1569; Gerth et al., 1996. J. Antibiotics 49(6): 560-563]

Epothilones show great potential in treating cancers. Although being structurally different, epothilones show very similar action mechanisms to those of well-known anti-cancer drug, paclitaxel (Taxol), including inducement of tubulin polymerization and stabilization of the formation of microtubes. These compounds exhibit powerful killing capability on different tumor cell lines. Specifically, they exhibit remarkable effects on multidrug-resistant (MDR) tumor cell lines, especially paclitaxel-resistant tumor cell lines or tumor cell lines having resistance to other anti-tumor drugs [Altmann et al., 2000. Biochem. Biophys. Acta. 1470(3): M79-91; Bollag et al., Cancer Res. 55(11): 2325-2333].
The deoxygenized counterparts of Epothilones A and B, namely Epothilones C and D, have been successfully synthesized via chemical total synthesis. However, they can also be obtained from the ferment extracts of natural epothilone-producing strain, S. cellulosum. They can be detected along with many other compounds with epothilone-like structures as trace components.
At present, attentions have been drawn to the development of epothilones and relevant analogues as more effective chemotherapeutants. For example, the naturally-occurring epothilone compounds may be modified by chemical semi-synthesis, such as the reaction converting Epothilone B into the corresponding lactam analogue BMS247550, as described in WO99/27890.
The new epothilone compounds of the present invention having the general formula (I) have beneficial pharmacologic properties, can inhibit the growth of tumor cells, and can be used in the treatment of proliferative disorders. They are prospective to become pioneer compounds for new anti-cancer drugs. Therefore, there is a good prospect for research and development of novel epothilone derivatives.